Evidence map›Paper›PMID 33772151›Full record

ArticleBritish journal of cancer2021

Interferon regulatory factor 1 (IRF-1) downregulates Checkpoint kinase 1 (CHK1) through miR-195 to upregulate apoptosis and PD-L1 expression in Hepatocellular carcinoma (HCC) cells.

Yihe Yan, Leting Zheng, Qiang Du, Xiao Cui, Kun Dong, Yarong Guo, David A Geller

Open access · hybridAbstract read
In one paragraph

Article in British journal of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
2.3field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

26 citing papers in PubMed, 34 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. The role of PD‑1/PD‑L1 axis in liver diseases.Clinical and experimental medicine · 2025
    Review
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. The Role of Interferon Regulatory Factors in Liver Diseases.International journal of molecular sciences · 2024
    Review
  11. Review
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
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  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 2 countries.

Yihe Yan *Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. yiheyan@hotmail.com.
Leting Zheng *Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Qiang DuThomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Xiao CuiThomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Kun DongThomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Yarong GuoThomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
David A GellerThomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. gellerda@upmc.edu.ORCID http://orcid.org/0000-0003-0735-1068
University of Pittsburgh Medical Center · USGuangxi Medical University · CN

Funding

Pittsburgh Liver Research CenterP30DK120531 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Gavin E Arteel · 2019 to 2026
$10.9M
NIDDK NIH HHS P30 DK120531NLM NIH HHS HHSN276201200017C
6 · The paper itself

Abstract

backgroundCHK1 is considered an oncogene with overexpression in numerous cancers. However, CHK1 signalling regulation in hepatocellular carcinoma (HCC) remains unclear.

methodsCHEK1 mRNA, protein, pri-miR-195 and miR-195 expression in HCC tissue was determined by qPCR, WB and IF staining assay. Survival analyses in HCC with high- and low-CHEK1 mRNA expression was performed using TCGA database. Relative luciferase activity was investigated in HCC cells transfected with p-CHEK1 3'UTR. Apoptosis was detected by TUNEL assay. NK and CD8+ T cells were analysed by flow cytometry.

resultsCHK1 is increased in human HCC tumours compared with non-cancerous liver. High CHK1 predicts worse prognosis. IFN-γ suppresses CHK1 via IRF-1 in HCC cells. The molecular mechanism of IRF-1 suppressing CHK1 is post-transcriptional by promoting miR-195 binding to CHEK1 mRNA 3'UTR, which exerts a translational blockade. Upregulated IRF-1 inhibits CHK1, which induces apoptosis of HCC cells. Likewise, CHK1 inhibition augments cellular apoptosis in HCC tumours. This effect may be a result of increased tumour NK cell infiltration. However, IRF-1 expression or CHK1 inhibition also upregulates PD-L1 expression via increased STAT3 phosphorylation.

conclusionsIRF-1 induces miR-195 to suppress CHK1 protein expression. Both increased IRF-1 and decreased CHK1 upregulate cellular apoptosis and PD-L1 expression in HCC.

Indexed as

AnimalsApoptosisB7-H1 AntigenCarcinoma, HepatocellularCell Line, TumorCell ProliferationCheckpoint Kinase 1FemaleHep G2 CellsHumansInterferon Regulatory Factor-1Liver NeoplasmsMiceMicroRNAsNeoplasm TransplantationPhosphorylationB7-H1 AntigenCD274 protein, humanCheckpoint Kinase 1CHEK1 protein, humanInterferon Regulatory Factor-1IRF1 protein, humanMicroRNAsMIRN195 microRNA, humanprexasertibPyrazinesPyrazolesSTAT3 protein, humanSTAT3 Transcription Factor

Identifiers

PMID33772151
PMCPMC8257880
OpenAlexW3137776635

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.